DIABETES MELLITUS by dr aftab ahmed
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Transcript of DIABETES MELLITUS by dr aftab ahmed
DIABETES DIABETES MELLITUSMELLITUS
DR AFTAB AHMED RAJPUT DR AFTAB AHMED RAJPUT FCPS PART 2 TRAINEE FCPS PART 2 TRAINEE
MEDICAL UNIT 2MEDICAL UNIT 2PMCH,NAWAB SHAHPMCH,NAWAB SHAH
PRESENTATION OUTLINES
DM AND ITS CLASSIFICATIONPATHOPHYSIOLOGY OF DMCLINICAL FEATURES OF DMINVESTIGATIONSDIAGNOSTIC CRITERIA FOR DM MANAGEMENT OF DM
DIABETES MELITUS…a metabolic disorder of multiple aetiology
characterised by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action or both
CURRENT IMPACT OF DM 66thth leading cause of death by disease leading cause of death by disease Decreases life expectancy of middle-aged people by Decreases life expectancy of middle-aged people by
5-10 years5-10 years• 2-4 x greater risk of death d/t heart disease2-4 x greater risk of death d/t heart disease
Compounding factors include: duration of disease, Compounding factors include: duration of disease, glycemic control, HTN, smoking, dyslipidemia, decreased glycemic control, HTN, smoking, dyslipidemia, decreased activity, and obesityactivity, and obesity
Leading cause of blindness in 25-74 year oldsLeading cause of blindness in 25-74 year olds Leading cause of non-traumatic amputationsLeading cause of non-traumatic amputations Responsible for 25-30% of all new dialysis patientsResponsible for 25-30% of all new dialysis patients
CLASSIFICATION OF DM
TRADITIONALY DM HAS BEEN DIVIDED INTO PRIMARY DM IN WHICH THERE IS DEFECT IN INSULIN PRODUCTION
AND/OR ITS ACTION 2NDRY IN WHICH ANY DISEASE CAUSES EXTENSIVE
DEMAGE OF PANCREATIC ISLET e.g,pancratitis,tumors,drugs,iron overload ,surgical removal of pancreatic substance and certain endocrinopathies that antagonize the action of insulin.
CLASSIFICATIONIn 1997 AMERICAN DIABETES ASSOCIATION
RECOMMENDED A NEW CLASSIFICATION BASED ON ETIOLOGY.
THERE IS NO DISTINCTION BETWEEN PRIMARY AND 2NDRY DM AND DESCRIPTION BASED ON AGE OF ONSET OR TYPE OF TREATMENT HAVE BEEN ELIMINATED.
CONTI……..1. Type 1 diabetes (b-cell destruction, leads to absolute insulin deficiency)
•Immune-mediated (TYPE 1A) •Idiopathic (TYPE 1B)2. Type 2 diabetes (insulin resistance with relative insulin deficiency)3. Genetic defects of b-cell function •Maturity-onset diabetes of the young (MODY), caused by mutations in:
•Hepatocyte nuclear factor 4a [HNF-4a] (MODY1)\•Glucokinase (MODY2)•Hepatocyte nuclear factor 1a [HNF-1a] (MODY3)•Insulin promoter factor [IPF-1] (MODY4)•Hepatocyte nuclear factor 1b [HNF-1b] (MODY5)•Neurogenic differentiation factor 1 [Neuro D1] (MODY6)•Mitochondrial DNA mutations
CONTI……4. Genetic defects in insulin processing or insulin action•Defects in proinsulin conversion•Insulin gene mutations•Insulin receptor mutations5. Exocrine pancreatic defects•Chronic pancreatitis•Pancreatectomy•Neoplasia•Cystic fibrosis•Hemachromatosis•Fibrocalculous pancreatopathy6. Endocrinopathies• Cushing syndrome• Hyperthyroidism• Pheochromocytoma• Glucagonoma• Acromegaly
CONTI……• 7. Infections• Rubella• Cytomegalovirus• Coxsackie virus B• Epstein barr virus• 8. Drugs Glucocorticoids interferon Protease inhibitors b-adrenergic agonists Thiazides Nicotinic acid9. Genetic syndromes associated with diabetes• Down syndrome• Kleinfelter syndrome• Turner syndrome• 10. Gestational diabetes mellitus
PATHOPHYSIOLOGGY OF DM• The pancreas functions as both an exocrine and an
endocrine gland• Exocrine function is associated with the digestive
system because it produces and secretes digestive enzymes
• Endocrine Function: produces two important hormones in Islets of Langerhans, insulin and glucagon– They work together to maintain a steady level of glucose, or sugar, in
the blood and to keep the body supplied with fuel to produce and maintain stores of energy.
Pancreatic Hormones• Insulin (beta cells)
– stimulates the uptake of glucose by body cells thereby decreasing blood levels of glucose
• Glucagon (alpha cells)– stimulates the breakdown of glycogen and the release of glucose, thereby
increasing blood levels of glucose
• Glucagon and insulin work together to regulate & maintain blood sugar levels
• Glycogen – Polysaccharide consisting of numerous monosaccharide glucoses linked
together. Stored as an energy source in liver & muscles
EFFECTS OF INSULIN
Regulation of Blood Sugar
High blood sugarHigh blood sugar Insulin
Pancreas Glycogen Glucose
Decreased
Glycogen synthase
IncreasedIncreased
Hormone
Signal TransductionSignal Transduction
Blood
LiverLiver
Low blood sugar Glucagon
GTP-protein-linked receptor
Tyrosine-kinase-linked receptor
Glycogen phosphorylase
Cori & Cori (1947)
Juang RH (2004) BCbasics
CONTIN…….– Type One Diabetes (10-15%)
• results when the body’s immune system destroys its own beta cells in the pancreas. No insulin production is then possible.
– Type Two Diabetes (85-90%)results from either
• Insulin resistance (overweight people)• Inadequate insulin production (lean people)• A combination of both
• Gestational Diabetes
Diabetes diagnosed during pregnancy Increased health risk to mother and babyMay require insulin injectionsGoes away after birth, but increased risk of developing Type 2 DM for mother and child
Diabetes diagnosed during pregnancy Increased health risk to mother and babyMay require insulin injectionsGoes away after birth, but increased risk of developing Type 2 DM for mother and child
Pathophysiology of type 1 diabetes
Pathophysiology of type 2 diabetes
Type Two Diabetes• Usually over 40 yrs of age though the age of diagnosis is
getting younger• Gradual onset with mild symptoms • Most produce a normal amount of insulin but it is unable to
work properly due to insulin resistance• Many have complications at diagnosis
What is Insulin Resistance?
• condition in which the body does not utilise insulin efficiently
• Insulin resistance is the decreased response of the liver and peripheral tissues (muscle, fat) to insulin– Insulin resistance is a primary defect in the
majority of patients with Type 2 diabetes
Insulin resistance syndrome(syndrome x,metabolic syndrome,REAVEN’S SYNDROME)• Metabolic syndrome is a name for a group of risk factors that occur
together and increase the risk for CAD, STROKE, and type 2 diabetes • The two most important risk factors for metabolic syndrome are: • Extra weight around the middle and upper parts of the body (central
obesity). The body may be described as "apple-shaped."• Insulin resistance, in which the body cannot use insulin effectively. Insulin
is needed to help control the amount of sugar in the body. As a result, blood sugar and fat levels rise.
• Other risk factors include:• Aging• Genes that make more likely to develop this condition • Hormone changes• Lack of exercise
• metabolic syndrome is present if ONE have three or more of the following signs:
• Blood pressure equal to or higher than 130/85 mmHg• Fasting blood sugar (glucose) equal to or higher than 100
mg/dL• Large waist circumference (length around the waist):
– Men - 40 inches or more– Women - 35 inches or more
• Low HDL cholesterol: – Men - under 40 mg/dL– Women - under 50 mg/dL
• Triglycerides equal to or higher than 150 mg/dL
• Tests that may be done to diagnose metabolic syndrome include:
• Blood pressure measurement• Glucose test• HDL cholesterol level• LDL cholesterol level• Total cholesterol level• Triglyceride level
Type 2 Diabetes Risk Factors• Increasing age• Obesity – especially abdominal
– Women with BMI > 35 compared to 22 have a 93 fold increased risk
– Men with BMI > 35 have 40 fold increased risk• Physical inactivity• Family history• Ethnic background• High blood pressure• High Cholesterol• Previous gestational diabetes
Characteristics of DiabetesType 1 Type 2• Usually under 30• Rapid onset• Normal or underweight• Little or no insulin • Ketosis common• Make up 15% of cases• Autoimmune plus environmental
factors• Low familial factor• Treated with insulin, diet and
exercise
• Usually over 40• Gradual onset • 80% are overweight• Most have insulin resistance• Ketosis rare• 85% of diagnosed cases• Part of metabolic insulin
resistance syndrome• Strongly hereditary• Diet & exercise, progressing to
tablets, then insulin
CLINICAL FEATURES OF DM
• Diabetes Mellitus Type 1
Clinical Manifestations:Polyuria – increased urinePolydipsia – increased thirstPolyphagia – increased hunger
3 ‘Ps”Weight lossFatigue Nausea, vomiting
Ketoacidosis may be a presenting sign
Clinical Manifestations:Polyuria – increased urinePolydipsia – increased thirstPolyphagia – increased hunger
3 ‘Ps”Weight lossFatigue Nausea, vomiting
Ketoacidosis may be a presenting sign
Diabetes Mellitus Type 1• Usually develop symptoms over a short period of time, and
the condition is often diagnosed in an emergency setting• In addition to high glucose levels, acutely ill
type 1 diabetics have high levels of ketones.– As cells cannot get glucose, they burn fats as an
alternate energy source– Ketones are produced by the breakdown of fat and
muscle, and are toxic at high levels– Ketones in the blood cause a condition called "acidosis”
or “ketoacidosis" (low blood pH)– Urine testing detects ketones in the urine– Blood glucose levels are also high.
Diabetes Mellitus Type 2
• Type 2 Clinical Manifestations:– Polydipsia – increased thirst– Polyuria – increased urine– Polyphagia – increased hunger– Fatigue– Blurred vision– Slow healing infections– Impotence in men
INVESTIGATION AND LABORATORY FINDINGS• URINALYSIS• BLOOD TESTING PROCEDURES• LIPOPROTEIN ABNORMALITIES IN DIABETES
URINALYSIS
• Urine glucose• Ketones• Protein(microalbuminia)
Blood tests
BLOOD GLUCOSEGLYCELATED HAEMOGLOBIN (HBA1C)BLOOD LIPIDS(TOTAL
CHOLESTROL,LDL,HDL,TRIGLYCERIDE)
Other test
• Routine blood count and coagulation screen• Arterial blood gases an any emergency like
diabetic ketoacidosis• Serum electrolyte and urea-creatinine• Lipid profile • Liver function test • Chest x ray• ECG
DIAGNOSTIC CRITERIA FOR DM
• Blood glucose levels - venous samples
• 1 sample is diagnostic if symptoms are present; 2 samples if asymtomatic:
– Fasting plasma glucose of > 7.0mmols(126MG/DL)
– Random plasma glucose of > 11.1mmols ( 200MG/DL)
– Plasma glucose of > 11.1(mmols (200MG/DL)2 hours after an oral glucose tolerance test (OGTT
GTT
• Venous Plasma • Fasting >126MG/DL DIABETES• Fasting 110MG/DL TO< 126MG/DL Impaired
Fasting Glycaemia• 2 hour level > 200MG/DL DIABETES• 2 hour 140MG/DL –200MG/DL Impaired
Glucose Tolerance
Impaired Fasting Glucose (IFG)
• Fasting plasma glucose > (100MG/DL)and (120) mmol/l
• Intermediate state between normal glucose tolerance and diabetes
• Present in 5% of the population and increasing with age
• Has greater risk CVD
Impaired Glucose Tolerance (IGT)• Fasting plasma glucose < 126MG/DLand OGTT 2 hour
value >140MG/DL but <200MG/DL• Intermediate state between normal glucose
tolerance and diabetes• Individuals often manifest hyperglycaemia only when
challenged with oral glucose in an OGTT• 2-5% of people with IGT progress to diabetes per
year• IGT associated with increase risk of developing
cardiovascular disease
MANAGEMENT OF DMMANAGEMENT OF DM
Cornerstones of Diabetes Management• Healthy eating• Exercise• Monitoring• Medication/Insulin• Health Care Team
Management of Diabetes
• Type One: Insulin + Healthy Eating + Exercise
• Type Two:• Healthy eating + exercise• then Healthy eating + exercise + tablets• then Healthy eating + exercise + tablets +
insulin
Diabetes MellitusDiabetes MellitusRole of Diet in Diabetic ManagementA. Goals for diabetic therapy include• 1. Maintain as near-normal blood glucose
levels as possible with balance of food with medications
• 2. Obtain optimal serum lipid levels• 3. Provide adequate calories to attain or
maintain reasonable weight
Diabetes MellitusB. Diet Composition• 1. Carbohydrates: 60 – 70% of daily diet
– Carbohydrates convert quickly to sugars• Advice patient to consume a similar amount of carbs at each
meal• Medications can work on a consistent glucose response from
foods
• 2. Protein: 15 – 20% of daily diet• 3. Fats: No more than 10% of total calories from
saturated fats
Diabetes Mellitus• 4. Fiber: 20 to 35 grams/day; promotes
intestinal motility and gives feeling of fullness• 5. Sodium: recommended intake 1000 mg per
1000 kcal• 6. Sweeteners approved by FDA instead of
refined sugars• 7. Limited use of alcohol: potential
hypoglycemic effect of insulin and oral hypoglycemics
Exercise & Weight Loss
• Benefits of a 10kg weight loss– Fall of 50% in fasting glucose– Fall of 10% total cholesterol– Fall of 15% LDL– Fall of 30% triglycerides– Rise of 8% HDL– Fall of 10 mmHg systolic, 20 mmHg
diastolic
SIGN guidelines
Oral HypoglycemicsOral Hypoglycemics
Oral Hypoglycemics All taken orally in the form of tablets.
Pts with type 2 diabetes have two physiological defects:
1. Abnormal insulin secretion2. Resistance to insulin action in target tissues
associated with decreased number of insulin receptors
Oral Anti-Diabetic Agents
SulfonylureasSulfonylureas Drugs other than Drugs other than
SulfonylureaSulfonylurea
Sulfonylureas (Oral Hypoglycemic drugs)Sulfonylureas (Oral Hypoglycemic drugs)
TolbutamideTolbutamide AcetohexamideAcetohexamide
TolazamideTolazamide
ChlorpropamideChlorpropamide GlipizideGlipizideGlyburideGlyburide
(Glibenclamide)(Glibenclamide)
GlimepirideGlimepiride
ShortShort
actingacting
First generationFirst generation
IntermediateIntermediate
actingacting
LongLong
actingacting
LongLong
actingacting
ShortShort
actingacting
Second generationSecond generation
Tolbutamid short-acting
Acetohexamideintermediate-
acting
Tolazamide intermediate-
acting
Chlorpropamide long- acting
Absorption Well Well Slow Well
Metabolism Yes Yes Yes Yes
Metabolites Inactive* Active +++ ** Active ++ ** Inactive **
Half-life 4 - 5 hrs 6 – 8 hrs 7 hrs 24 – 40 hrs
Duration of action
Short (6 – 8 hrs)
Intermediate (12 – 20 hrs)
Intermediate (12 – 18 hrs)
Long( 20 – 60 hrs)
Excretion Urine Urine Urine Urine
FIRST GENERATION SULPHONYLUREA COMPOUNDS
* Good for pts with renal impairment Good for pts with renal impairment
** Pts with renal impairment can expect long t1/2
GlipizideShort- acting
Glibenclamide(Glyburide)Long-acting
GlimepirideLong-acting
Absorption Well Well WellMetabolism Yes Yes YesMetabolites Inactive Inactive InactiveHalf-life 3 – 4 hrs Less than 3 hrs 5 - 9 hrsDuration of action
10 – 16 hrs 12 – 24 hrs 12 – 24 hrs
Excretion Urine Urine Urine
SECOND GENERATION SULPHONYLUREA COMPOUNDS
MECHANISM OF ACTION OF SULPHONYLUREAS
1) Release of insulin from β-cells
2) Reduction of serum glucagon concentration
3) Potentiation of insulin action on target tissues
SIDE EFFECTS OF SULPHONYLUREAS
1) Nausea, vomiting, abdominal pain, diarrhea
2) Hypoglycaemia
3) Dilutional hyponatraemia & water intoxication (Chlorpropamide)
4) Weight gain
CONTRAINDICATIONS OF SULPHONYLUREAS
1) Type 1 DM ( insulin dependent)
2) Parenchymal disease of the liver or kidney
3) Pregnancy, lactation
4) Major stress
Drugs other than Sulfonylurea Drugs other than Sulfonylurea
MetforminMetformin
BiguanidesBiguanides α-Glucosidaseα-Glucosidase
InhibitorsInhibitors
ThiazolidinedionesThiazolidinediones
AcarboseAcarbose RosiglitazoneRosiglitazone
PioglitazonePioglitazone
RepaglinideRepaglinide
NateglinideNateglinide
MeglitinidesMeglitinides
MEGLITINIDES
e.g. Repaglinide, Nateglinide
PHARMACOKINETICS
Taken orally
Rapidly absorbed ( Peak approx. 1hr )
Metabolized by liver
t1/2 = 1 hr
Duration of action 4-5 hr
MEGLITINIDES (Contd.)
MECHANISM OF ACTION
Bind to the same KATP Channel
as do Sulfonylureas,
to cause insulin release from β-cells.
MEGLITINIDES (Contd.)
CLINICAL USE
Approved as monotherapy and in combination with metformin in type 2 diabetes
Taken before each meal, 3 times / day
Does not offer any advantage over sulfonylureas;
Advantage: Pts. allergic to sulfur or sulfonylurea
SIDE EFFECTS:
Hypoglycemia
Wt gain ( less than SUs )
Caution in pts with renal & hepatic impairement.
BIGUANIDES e.g. Metformin
PHARMACOKINETICS
Given orally
Not bind to plasma proteins
Not metabolized
Excreted unchanged in urine
t 1/2 2 hr
BIGUANIDES (Contd.)
MECHANISM OF ACTION
1. Increase peripheral glucose utilization
2. Inhibits gluconeogenesis
3. Impaired absorption of glucose from the gut
Advantages of Metformin over SUs
Does not cause hypoglycemia Does not result in wt gain ( Ideal for obese pts )
BIGUANIDES (Contd.)
SIDE EFFECTS
1. Metallic taste in the mouth
2. Gastrointestinal (anorexia, nausea, vomiting,
diarrhea, abdominal discomfort)
3. Vitamin B 12 deficiency (prolonged use)
4. Lactic acidosis ( rare – 01/ 30,000-exclusive in
renal & hepatic failure)
1. Hepatic impairment
2. Renal impairment
3. Alcoholism
4. Heart failure
BIGUANIDES (Contd.)
CONTRAINDICATIONS
1. Obese patients with type 11 diabetes
2. Alone or in combination with sulfonylureas
BIGUANIDES (Contd.)
INDICATIONS
α-GLUCOSIDASE INHIBITORS
e.g. Acarbose
PHARMACOKINETICS
Given orally
Not absorbed from intestine except small amount
t1/2 3 - 7 hr
Excreted with stool
MECHANISM OF ACTION
Inhibits intestinal alpha-glucosidases and
delays carbohydrate absorption, reducing postprandial increase in blood glucose
α-GLUCOSIDASE INHIBITORS(Contd.)
SIDE EFFECTS
Flatulence
Loose stool or diarrhea
Abdominal pain
Alone does not cause hypoglycemia
α-GLUCOSIDASE INHIBITORS(Contd.)
INDICATIONS
Patients with Type 11 inadequately controlled by diet with or without other agents( SU, Metformin)
Can be combined with insulin
may be helpful in obese Type 11 patients (similar to metformin)
α-GLUCOSIDASE INHIBITORS(Contd.)
THIAZOLIDINEDIONE DERIVATIVES
New class of oral antidiabetics
e.g.: Rosiglitazone
Pioglitazone
PHARMACOKINETICS
- 99% absorbed
- Metabolized by liver
- 99% of drug binds to plasma proteins
- Half-life 3 – 4 h
- Eliminated via the urine 64% and feces 23%
THIAZOLIDINEDIONE DERIVATIVES(Contd.)
MECHANISM OF ACTION
- Increase target tissue sensitivity to insulin by: reducing hepatic glucose output & increase
glucose uptake & oxidation in muscles & adipose tissues.
They do not cause hypoglycemia (similar to metformin and acarbose ) .
THIAZOLIDINEDIONE DERIVATIVES(Contd.)
ADVERSE EFFECTS
- Mild to moderate edema
- Wt gain
- Headache
- Myalgia
- Hepatotoxicity
THIAZOLIDINEDIONE DERIVATIVES(Contd.)
INDICATIONS
Type 11 diabetes alone or in combination with
metformin or sulfonylurea or insulin in patients
resistant to insulin treatment.
THIAZOLIDINEDIONE DERIVATIVES(Contd.)
DPP-4 Inhibitor• Inhibits the dipeptidyl-peptidase 4 enzyme• Enhances the incretin hormones• GLP-1 (Glucagon-like peptide 1)• GIP (glucose-dependent insulinotropic
polypeptide)
Incretin HormonesStimulate insulin response from Stimulate insulin response from beta cells in a glucose-dependent mannerbeta cells in a glucose-dependent manner
Inhibit gastric emptyingInhibit gastric emptying
Reduces food intake and body weightReduces food intake and body weight
Inhibit glucagon secretion from Inhibit glucagon secretion from alpha cells in a glucose-dependent manneralpha cells in a glucose-dependent manner
DPP-4 Inhibitor• Available product: Januvia (Sitagliptin)• Once daily dosing• Indicated for use with metformin or
thiazolidinedione• Dosing adjustment for renal impairment• Adverse effects: Diarrhea, upper respiratory infection• Expensive
INSULIN THERAPHYINSULIN THERAPHY
Diabetes MellitusDiabetes MellitusMedications
A. Insulin• 1. Sources: standard practice is use of human insulin prepared by
alteration of pork insulin or recombinant DNA therapy2. Clients who need insulin as therapy:• a. All type 1 diabetics since their bodies essentially no longer
produce insulin• b. Some Type 2 diabetics, if oral medications are not adequate for
control (both oral medications and insulin may be needed)• c. Diabetics enduring stressor situations such as surgery,
corticosteroid therapy, infections, treatment for DKA • d. Women with gestational diabetes who are not adequately
controlled with diet • e. Some clients receiving high caloric feedings including tube
feedings or parenteral nutrition
• Insulin Degradation• Hydrolysis of the disulfide linkage between A&B
chains.• 60% liver, 40% kidney(endogenous insulin)• 60% kidney,40% liver (exogenous insulin)• Half-Life 5-7min (endogenous insulin) Delayed-release form( injected one)• Category B ( not teratogenic)• Usual places for injection: upper arm, front& side
parts of the thighs& the abdomen.• Not to inject in the same place ( rotate)• Should be stored in refrigerator& warm up to
room temp before use.• Must be used within 30 days.
TYPES OF INSULIN PREPARATIONS
1. Ultra-short-acting
2. Short-acting (Regular)
3. Intermediate-acting
4. Long-acting
3. Intermediate - acting insulins
e.g. isophane (NPH)
Turbid suspension
Injected S.C.(Only)
Onset of action 1 - 2 hr
Peak serum level 5 - 7 hr
Duration of action 13 - 18 hr
Insulin mixtures
75/25 70/30 50/50 ( NPH / Regular )
3. Intermediate - acting insulins (contd.)
Lente insulin
Turbid suspension
Mixture of 30% semilente insulin
70% ultralente insulin
Injected S.C. (only)
Onset of action 1 - 3 hr
Peak serum level 4 - 8 hr
Duration of action 13 - 20 hr
3. Intermediate - acting insulins (contd.)
Lente and NPH insulins
Are roughly equivalent in biological effects.
They are usually given once or twice a day.
N.B: They are not used during emergencies
(e.g. diabetic ketoacidosis).
4. Long – acting insulins e.g.Insulin glargine
Onset of action 2 hr
Absorbed less rapidly than NPH&Lente insulins.
Duration of action upto 24 hr
Designed to overcome the deficiencies of intermediate acting insulins
Advantages over intermediate-acting insulins:Constant circulating insulin over 24hr with no pronounced peak.
More safe than NPH&Lente insulins due to reduced risk of hypoglycemia(esp.nocturnal hypoglycemia).
Clear solution that does not require resuspention before administration.
Methods of Adminisration• Insulin Syringes• Pre-filled insulin pens• External insulin pump
Under Clinical Trials• Oral tablets• Inhaled aerosol• Intranasal, Transdermal • Insulin Jet injectors• Ultrasound pulses
COMPLICATIONS OF INSULIN THERAPY
1. Severe Hypoglycemia (< 50 mg/dl )– Life threatening
Overdose of insulin
Excessive (unusual) physical exercise
A meal is missed
2. Weight gain
3. Local or systemic allergic reactions (rare)
4. Lipodystrophy at injection sites
5. Insulin resistance
6. Hypokalemia